Gargling with Ketamine Attenuates the Postoperative Sore Throat

Summary Postoperative sore throat (POST) is a common complication of anaesthesia with endotracheal tube that affects patient satisfaction after surgery. Therefore, this complication remains to be resolved in patients undergoing endotracheal intubation. The aim of the study was to compare theeffectiveness of ketamine gargleswith placebo in prevent-ing POST after endotracheal intubation. Forty patients scheduled for elective surgery under general anaesthesia were randomized into : Group C, water 30 ml; Group K, ketamine 50 mg in water 29 ml. Patients were asked to gargle this mixture for 40 seconds, 5 minutes before induction of anaesthesia. POST was graded at 4,8 and 24 hours after operation on a four-point scale (0-3). In the Control group POST occurred more frequently, when compared with patients belonging to Ketamine group, at 4, 8, and 24 hours and significantly more patients suffered severe POST in Control group at 8 and 24 hours compared with Ketamine group ( P <0.05). We demonstrated that gargling with ketamine significantly attenuated POST, with no drug-related side effects were observed.


Introduction
Recently, quality assurance of anaesthesia has become increasingly important for improving postoperative outcome. Postoperative sore throat (POST) is a minor complication that is unresolved in patients undergoing endotracheal intubation [1][2][3][4][5][6][7] .POSTwas recently ranked by American anaesthesiologists as the eighth m ost im po rtan t problem of current clinical anaesthesiology 8 . POST followingtracheal intubation is due to trauma to the airway mucosa. The reported incidence of POST varies from 21 to 65% 2,9,10 . Various pharmacological and non -pharmacological trials have been used for attenuating POST with variable success. The pharmacological methods include beclamethasoneinhalation andgarglingwithazulene sulfonate 11,12 . It has been shown that NMDA receptors are present not only in the centralnervous system but also in the peripheralnerves 13,14 . It has been further reported that peripherally administered NMDAreceptor antago-nistsare involvedwith antinociception 15 and anti-inflammatory cascade 16 .
In this study, we investigated whether preoperative garglingwith ketamine, a NMDA receptor antagonist, reduced POSTafter orotrachealintubation and compared with placebo.

Methods
Written informed consent was obtained from 40healthy youngpatients undergoingabdominal and pelvic surgery under general anaesthesia. There were no restrictionson recruitingthe patientsby type of surgery. The study was conducted in a prospective, randomized, placebo-controlled, and single -blinded manner. Patients with anticipated airway difficulty, history of preoperative sore throat and asthma, known sensitivity to study drug or recent anti-inflammatory medicationwere excludedfrom thestudy. Furthermore, patients with upper respiratory tract disease were also excluded from this study. Patients requiringmore than oneattempt forpassage of trachealtube were excluded from the study. Patients in whom extubation provoked buckingor coughingwere alsoexcluded from the study.
Presuming the incidence of POST to be 60%, the power analysis 17 (taking = 0.05 and = 0.90) calculated a sample size of 20 patients in each of the two groups to show a 50% reduction in the incidence. Hence, we chose to enroll 20 patients in each group.
Premedication consisted of tabletalprazolam 0.25 mg orally three hours beforesurgery. Patients were randomly assigned (by meansof arandom numbertable) in a single-blind manner into oneof twogroups according to the agent used for gargle. Group C received drinking water 30 ml and Group K received preservative free ketamine 1 ml(50 mg) in 29ml of drinking waterby the operation theatre nurseand askedpatients togargle with the preparation for 40seconds after their arrival in the operation room.Anaesthesia wasinduced 5minutes later. The patientscould not be blinded because of the different tastes of the two preparations.
Standard non-invasive monitoring was done throughoutthe anaesthesia.Followingpreoxygenation, induction ofanaesthesiawasdonewithfentanyl 2mcg.kg -1 and 2 mg.kg -1 of propofol sufficient to obtund the eyelash reflex, followedby atracurium 0.5mg.kg -1 to facilitateorotrachealintubationwith sterile polyvinylchloride endotracheal tube (having low pressure cuffs) with an internaldiameter of 7.5 mm for women and 8.5mm for men. Trachealintubation was performed by an experienced anaesthesiologist havingexperience of >3 years. The endotrachealtubes werelubricated with sterile water at room temperature. Immediately after intubation, cuff ofthe endotrachealtubes were filled witha volume of room air required to prevent an audible air leak. Anaesthesiawas maintainedwith oxygen33% innitrous oxide, supplemented with halothane. Supplemental analgesia during surgery was provided with smalldoses of intravenousfentanyl. Residualneuromuscular relaxation with atracurium was antagonized with neostigmine and glycopyrrolate on completion ofsurgery. Oropharyngeal suction before extubation was done underdirect vision to avoid trauma to the tissues, confirmingthat secretion clearance was complete 18 .
The patients were interviewed in a standard fashion by a blinded investigator at 4,8, and 24hours after the procedure. POST was graded on a four point scale (0-3) : 0, no sore throat; 1 , mild sore throat (complains of sore throat only on asking) ; 2, moderate sore throat (complains of sore throat on his/her own) ; 3, severe sore throat (change of voice or hoarseness, associated with throat pain 19 ). Other side-effects, if any, were also noted.
To compare patient characteristics, including age, height, body weight, and duration of anaesthesia and surgery student's t-test was performed. The Mannwhitney U-test was used for multiple paired comparisons of counts in patients with POST. P< 0.05 was consideredstatistically significant.

Discussion
In the Control group , the incidence of POST 4, 8, and 24 hours after surgery was 85%, 75%, and 60% respectively ( Table 2). The reported incidence of POST is between 45 and more than 90% 4,5,18,19 . Our result in the Control group was consistent with previous findings. In ourstudy, the incidence wassignificantly lower in theKetamine group than in the Controlgroup. There were no adverse reactions in the ketamine group. This is the first report of the efficacy of gargling with Ketamine in reducingPOST in our country.
Sore throat related to orotracheal tube might be consequence of localized trauma,leading to aseptic inflammation of pharyngealmucosa. It may also be associated with oedema, congestion, and pain 2,25 . Reduction ofthis inflammationby ketamine gargling may be the reason for decreased in POST in our study. However, aperipheral andcentral action following systemic absorption cannot be excluded.
The antiinflammatoryproperties ofketamine have been shown against lung injury 26 . Moreover, ketamine has been shownto diminishthe expression of inducible nitric oxide synthase 27 . Further, in an animalstudy, it hasbeenshown thatnebulizedketamineattenuated many of the centralcomponent of inflammatory changes 16 .